CPSF1 p.Pro688=
c.2064G>A · VCV4902096
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.223%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -4.9 | GERP -4.1 |
| Overall | ||
| CADD | 2.321 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.223%
African / African-American · 167/74,990 alleles
Filtering AF
0.195%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.184%
Overall
0.0239%
384/1,608,026 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.223% | 449 |
| East Asian | 0.0781% | 1,280 |
| Middle Eastern | 0.0496% | 2,015 |
| Admixed American | 0.0485% | 2,064 |
| Remaining individualsnot grpmax-eligible | 0.0321% | 3,117 |
| European (non-Finnish) | 0.0109% | 9,134 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0034% | 29,448 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- CPSF1
- Protein
- p.Pro688=
- Coding
- c.2064G>A
- MANE Select
- NM_013291
- Type
- single nucleotide variant
- Location
- chr8:144397963 (GRCh38)
- Gene constraint
- LOEUF 0.74 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.97 · 13 PDB
- Residue 688
- a UniProt-annotated variant site (in myp27)
Similar variants
- CPSF1 p.Pro688Leu Uncertain significance ★ ⚠ same residue
- CPSF1 p.Ala1319Thr Uncertain significance ★★ ⚠ same type
- CPSF1 p.Thr561Ile Uncertain significance ★★ ⚠ same type
- CPSF1 p.Gly722= Likely benign ★★ same type
- CPSF1 p.Leu1360= Likely benign ★★ same type
- CPSF1 p.Pro438= Likely benign ★★ same type
- CPSF1 p.Pro654= Likely benign ★★ same type
- CPSF1 c.539+1G>A Likely pathogenic ★ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cpsf1-p-pro688 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown